Cell-Based NIPT Detects 47,XXY Genotype in a Twin Pregnancy

Line Dahl Jeppesen; Tina Duelund Hjortshøj; Johnny Hindkjær; Lotte Hatt; Olav Bjørn Petersen; Ripudaman Singh; Palle Schelde; Lotte Andreasen; Rikke Christensen; Dorte L Lildballe; Ida Vogel

doi:10.3389/fgene.2022.842092

Cell-Based NIPT Detects 47,XXY Genotype in a Twin Pregnancy

Front Genet. 2022 Mar 11:13:842092. doi: 10.3389/fgene.2022.842092. eCollection 2022.

Authors

Line Dahl Jeppesen^{1

2}, Tina Duelund Hjortshøj³, Johnny Hindkjær⁴, Lotte Hatt¹, Olav Bjørn Petersen^{5

6}, Ripudaman Singh¹, Palle Schelde¹, Lotte Andreasen⁷, Rikke Christensen⁷, Dorte L Lildballe^{2

8}, Ida Vogel^{2

7}

Affiliations

¹ ARCEDI, Vejle, Denmark.
² Center for Fetal Diagnostics, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
³ Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
⁴ Aagaard Fertility Clinic, Aarhus, Denmark.
⁵ Center for Fetal Medicine, Department of Obstetrics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
⁶ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
⁷ Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.
⁸ Department of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus, Denmark.

Abstract

Background: The existing risk of procedure-related miscarriage following invasive sampling for prenatal diagnosis is higher for twin pregnancies and some women are reluctant to test these typically difficultly obtained pregnancies invasively. Therefore, there is a need for noninvasive testing options that can test twin pregnancies at an early gestational age and ideally test the twins individually. Case presentation: A pregnant woman opted for cell-based NIPT at GA 10 + 5. As cell-based NIPT is not established for use in twins, the test was provided in a research setting only, when an ultrasound scan showed that she carried dichorionic twins. Materials and Methods: Fifty mL of peripheral blood was sampled, and circulating fetal cells were enriched and isolated. Individual cells were subject to whole-genome amplification and STR analysis. Three fetal cells were analyzed by chromosomal microarray (aCGH). Results: We identified 20 fetal cells all sharing the same genetic profile, which increased the likelihood of monozygotic twins. aCGH of three fetal cells showed the presence of two X chromosomes and a gain of chromosome Y. CVS from both placentae confirmed the sex chromosomal anomaly, 47,XXY and that both fetuses were affected. Conclusion: NIPT options can provide valuable genetic information to twin pregnancies that help the couples in their decision-making on prenatal testing. Little has been published about the use of cell-based NIPT in twin pregnancies, but the method may offer the possibility to obtain individual cell-based NIPT results in dizygotic twins.

Keywords: cell-based NIPT; cell-free NIPT; circulating fetal cells; extravillous trophoblasts; klinefelter syndrome; sex chromosome anomaly; twin pregnancy.